Project Summary/Abstract Osteochondritis Dissecans (OCD)/Osteochondrosis (OC) is an important orthopaedic disease in children; however, the etiology and pathogenesis remain unclear. OCD/OC is highly prevalent (nearly 100% affected) in growing pigs causing lameness. Previous work by our group has demonstrated that the pathogenesis of OCD/OC in pigs involves failure of cartilage canal blood supply, with resulting necrosis of epiphyseal (growth) cartilage. We hypothesize that the pathogenesis of OC/OCD in children is similar; however, the relationship between failed cartilage canal blood supply and osteochondritis dissecans (OCD) in people has not been studied due to 1) lack of noninvasive imaging techniques to visualize these structures in vivo and 2) limited access to appropriate post mortem tissues. We have developed a unique collaboration among magnetic resonance imaging (MRI) experts and veterinary and human orthopaedic researchers that will make use of the exceptional resources at the Center for Magnetic Resonance Research at the University of Minnesota to fill in the above mentioned gaps in knowledge. Our group recently developed and validated MRI methods to identify cartilage canal blood vessels and ischemic necrosis of the epiphyseal cartilage in young pigs. We wish to extend these studies to children and adolescents to investigate the maturation process of the articular- epiphyseal cartilage of the distal femur noninvasively in humans and compare it to that occurring in swine. This will be accomplished by the completion of four specific aims. Aims 1 and 2 focus on the development/ implementation/validation of novel MRI techniques, ex vivo, to image the vascular supply and cartilage matrix characteristics/morphology in cadaveric specimens from normal children and from young pigs in which subclinical lesions of osteochondrosis will be present (allowing evaluation of normal tissues as well as of areas of cartilage necrosis). Aims 3 and 4 focus on the development and testing of a rapid pediatric imaging protocol for in vivo studies in normal children and children first diagnosed with OCD. This research will have multiple benefits by 1) validating swine as a highly appropriate animal model of this important human disease, 2) providing a method to diagnose the disease at an early point in its development at which time treatments are likely to be effective, and 3) greatly improving our understanding of the pathophysiology of the disease.